2022
Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas
Zhang H, Li B, Huang Q, López-Giráldez F, Tanaka Y, Lin Q, Mehta S, Wang G, Graham M, Liu X, Park I, Eichmann A, Min W, Zhou J. Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas. Nature Communications 2022, 13: 7637. PMID: 36496409, PMCID: PMC9741628, DOI: 10.1038/s41467-022-35262-w.Peer-Reviewed Original ResearchConceptsMitochondrial dysfunctionThioredoxin 2Single-cell RNA-seq analysisRNA-seq analysisMutant miceNuclear genesMitochondrial proteinsMitochondrial localizationHuman retinal diseasesTranscriptional factorsGene expressionMutant retinasMitochondrial activityExtracellular matrixNovel mechanismVascular maturationArteriovenous malformationsGenetic deficiencyVessel growthSmad2Mouse retinaVascular malformationsMechanistic studiesBasement membraneRetinal vascular malformations
2020
Chronic mTOR activation induces a degradative smooth muscle cell phenotype
Li G, Wang M, Caulk AW, Cilfone NA, Gujja S, Qin L, Chen PY, Chen Z, Yousef S, Jiao Y, He C, Jiang B, Korneva A, Bersi MR, Wang G, Liu X, Mehta S, Geirsson A, Gulcher JR, Chittenden TW, Simons M, Humphrey JD, Tellides G. Chronic mTOR activation induces a degradative smooth muscle cell phenotype. Journal Of Clinical Investigation 2020, 130: 1233-1251. PMID: 32039915, PMCID: PMC7269581, DOI: 10.1172/jci131048.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAortic Aneurysm, ThoracicAortic DissectionBeta CateninDisease Models, AnimalLysosomesMechanistic Target of Rapamycin Complex 1MiceMice, Knockout, ApoEMicrophthalmia-Associated Transcription FactorMyocytes, Smooth MuscleSignal TransductionTOR Serine-Threonine KinasesTuberous Sclerosis Complex 1 ProteinConceptsMTOR activationMTOR complex 1Smooth muscle cell phenotypeMuscle cell phenotypeContext of hyperlipidemiaSmooth muscle cell proliferationThoracic aortic aneurysmDegradative organellesMuscle cell proliferationHematopoietic lineage markersSMC phenotypeLysosomal clearanceAdvanced diseaseMedial degenerationAortic diseaseLysosomal markersAortic aneurysmExtracellular matrixPhenotypic modulationConventional macrophagesMacrophage markersMedial SMCsConditional disruptionLineage markersImmune effectors
2019
Histone H2B monoubiquitination regulates heart development via epigenetic control of cilia motility
Robson A, Makova SZ, Barish S, Zaidi S, Mehta S, Drozd J, Jin SC, Gelb BD, Seidman CE, Chung WK, Lifton RP, Khokha MK, Brueckner M. Histone H2B monoubiquitination regulates heart development via epigenetic control of cilia motility. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 14049-14054. PMID: 31235600, PMCID: PMC6628794, DOI: 10.1073/pnas.1808341116.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementCell ProliferationChromatin Assembly and DisassemblyCiliaDisease Models, AnimalEpigenesis, GeneticGene Expression Regulation, NeoplasticHeartHeart Defects, CongenitalHistonesHumansLoss of Function MutationMiceRegulatory Factor X Transcription FactorsSignal TransductionUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesUbiquitinationXenopusConceptsHistone H2B monoubiquitinationCilia genesH2B monoubiquitinationCilia motilityFunctional gene ontologyHuman congenital heart diseaseUpstream transcriptional regulatorsTissue-specific expressionChromatin remodeling genesChromatin remodelingEpigenetic controlH2Bub1 levelsTranscriptional regulatorsChIP-seqDepletion phenotypeGene OntologyGenomic analysisTranscription factorsKnockdown resultsLeft-right asymmetryCilia functionHeart developmentH2Bub1RNF20Complex consisting
2018
Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira
Adhikarla H, Wunder EA, Mechaly AE, Mehta S, Wang Z, Santos L, Bisht V, Diggle P, Murray G, Adler B, Lopez F, Townsend JP, Groisman E, Picardeau M, Buschiazzo A, Ko AI. Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira. Frontiers In Cellular And Infection Microbiology 2018, 8: 45. PMID: 29600195, PMCID: PMC5863495, DOI: 10.3389/fcimb.2018.00045.Peer-Reviewed Original ResearchConceptsResponse regulatorTwo-component system proteinsDNA-binding response regulatorGlobal transcriptional regulationHybrid histidine kinaseGlobal gene regulationNovel signal pathwayComprehensive genomic analysisPhosphotransfer assaysTCS genesHistidine kinaseGene duplicationTranscriptional regulationGene regulationCorresponding genesPhylogenetic analysisGenomic analysisMolecular basisMutant strainSystem proteinsSignaling systemInfection processGenesBranched pathwayVirulence